Dichloromethane → Dichloromethane methanol ammonium hydroxide
Reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]([NH:12][C:13](=O)[O:14]CC3C4C=CC=CC=4C4C3=CC=CC=4)[CH3:11])[N:7]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:6]=2[CH:37]=1.N1CCCCC1.[CH2:44]([Cl:46])[Cl:45]>>[CH2:44]([Cl:46])[Cl:45].[CH3:13][OH:14].[NH4+:7].[OH-:14].[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]([NH2:12])[CH3:11])[N:7]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:6]=2[CH:37]=1Participants
Procedure
To a solution of (9H-fluoren-9-yl)methyl 1-(6-fluoro-1-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)ethylcarbamate (3.38 g, 6.82 mmol) in DCM (34.1 mL) was added piperidine (0.809 mL, 8.19 mmol) and the mixture was stirred at rt. After 4 days, the mixture was concentrated under reduced pressure to give a brown solid. The brown solid was purified by column chromatography on a 120 g of Redi-Sep column using 0 to 100% gradient of DCM:MeOH:NH4OH (89:9:1) in DCM over 27 min and then 100% isocratic of DCM:MeOH:NH4OH (89:9:1) for 5 min as eluent to give 1-(6-fluoro-1-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)ethanamine over three steps as a pink syrupy solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.67 (3H, td, J=8.8, 5.0 Hz), 7.48 (2H, t, J=8.8 Hz), 7.09 (1H, ddd, J=9.8, 8.8, 2.5 Hz), 6.88 (1H, dd, J=9.0, 2.3 Hz), 3.93 (1H, q, J=6.8 Hz), 1.92 (2H, br. s.), 1.33 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 274.0 [M+H]+.
Workup
- concentrationthe mixture was concentrated under reduced pressure
- customto give a brown solid
- customThe brown solid was purified by column chromatography on a 120 g of Redi-Sep column
- customover 27 min
Sources & evidence
- ORD record
- ord-b90e0a94f18b472db063c20fb35d7e3c
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08575183B2
Reaction notes
Loading…